The proposed research is aimed at developing saccharide-peptide hybrid copolymers as a family of fundamentally new versatile polymeric biomaterials. The development of new generations of highly functional, well-defined and "interactive" biomaterials is essential to advance the field of tissue engineering towards a viable clinical reality. Despite this, very few truly novel biomaterials have emerged, with most researchers instead focusing their efforts to modify materials that have been studied for the past 20-30 years. While this approach has achieved certain extent of successes, many of the existing materials suffer from significant limitations and are unable to predictably control cell function. As an alternative, this multi-disciplinary research proposal seeks to develop and test truly novel polymeric biomaterials. Recent breakthroughs in the Guan laboratory led to a series of novel biomaterials derived from peptide and saccharide starting materials. In vitro tests show that the saccharide-peptide hybrid copolymers can be degraded by proteolysis and have low cytotoxicity. Preliminary animal studies indicate these materials do not illicit systemic immune response in rats. These features combined with their versatility and high functionality make these biomaterials promising candidates for interactive biomaterials applications. In this proposal, we will leverage the synthetic chemistry expertise of the Guan laboratory to develop bio-interactive materials, and the cell biology expertise of the Putnam laboratory to investigate these new materials as synthetic extracellular matrix (ECM) analogs. Specifically, we propose to develop efficient synthesis of novel saccharide-peptide hybrid copolymers and test the in vitro and in vivo biocompatibility of these new materials. Through the proposed studies the following specific aims will be accomplished: (1) we will develop efficient and benign synthetic routes for making saccharide-peptide hybrid copolymers and their hydrogels;(2) we will prepare and characterize a series of well-defined hydrogel matrices having precisely controlled chemical and mechanical properties;(3) we will investigate the cytocompatibility of these hydrogel materials as model substrates for cell studies, and address their ability to direct cell phenotype in vitro;and finally (4) we will investigate their in vivo compatibility and potential as cell delivery vehicles.